Incidence and characteristics of post-COVID-19 parkinsonism and dyskinesia related to COVID-19 vaccines.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an infectious disease mainly affecting the respiratory system; however, a significant prevalence of neurological symptoms has been noted. OBJECTIVES: To investigate the incidence and characteristics of post-COVID-19 parkinsonism and to study dyskinesia related to COVID-19 vaccines. MATERIAL AND METHODS: The MEDLINE, PubMed, Scopus, and Web of Science databases were searched for all manuscripts relevant to post-COVID-19 parkinsonism and dyskinesia related to COVID-19 vaccines. Subsequently, we extracted and analysed data from the manuscripts in a structured manner. RESULTS: We found 24 patients with post-COVID-19 parkinsonism, with a mean onset age of 58 years after a mean of 30 days from the COVID-19 onset. Akinetic-rigid (n = 11) and mixed (n = 6) subtypes were the most common. Asymmetry was present in 13/15 patients. Brain MRI was unremarkable in 11/19, whereas dopaminergic system imaging was abnormal in 8/8 patients. Responsiveness to dopaminergic treatment was observed in 12/15 patients. Four patients improved after immunomodulatory therapy. Comorbidities were present in 9/24, encephalopathy symptoms in 11/24, and loss of smell in 9/13 patients. Most patients (n = 14) suffered serious COVID-19- related complications and three were treated with haloperidol. Parkinsonism improved (n = 5) or resolved (n = 4) during the follow-up. Five patients, with a mean age of 52, developed dyskinesia at a mean of 25 hours after receiving the COVID-19 mRNA vaccines. One patient had a history of neuropsychiatric symptoms and developed functional dyskinesia of the tongue. Four patients had a previous history of Parkinson's Disease (PD) with a mean duration of 10 years and developed dyskinesia and dystonia, which resolved (n = 2) or improved (n = 2) during the follow-up. CONCLUSIONS: Post-COVID-19 parkinsonism is a very rare complication, and it is likely that this is an umbrella syndrome that includes many different etiologies. Dyskinesia due to COVID-19 vaccines is exceedingly rare and probably has the same pathophysiological basis as in other conditions with exacerbation of PD symptoms.

Viruses, parkinsonism and Parkinson's disease: the past, present and future.

Parkinsonism secondary to viral infections is not an uncommon occurrence and has been brought under the spotlight with the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A variety of viruses have been described with a potential of inducing or contributing to the occurrence of parkinsonism and Parkinson's disease (PD), although the relationship between the two remains a matter of debate originating with the description of encephalitis lethargica in the aftermath of the Spanish flu in 1918. While some viral infections have been linked to an increased risk for the development of PD, others seem to have a causal link with the occurrence of parkinsonism. Here, we review the currently available evidence on viral-induced parkinsonism with a focus on potential pathophysiological mechanisms and clinical features. We also review the evidence on viral infections as a risk factor for developing PD and the link between SARS-CoV-2 and parkinsonism, which might have important implications for future research and treatments.

Post-COVID-19 Parkinsonism and Parkinson's Disease Pathogenesis: The Exosomal Cargo Hypothesis.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer's disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting. Exosomes are extracellular nanovesicles bearing a complex cargo of active biomolecules and playing crucial roles in intercellular communication under pathophysiological conditions. Exosomes constitute a reliable route for misfolded protein transmission, contributing to PD pathogenesis and diagnosis. Herein, we summarize recent evidence suggesting that SARS-CoV-2 infection shares numerous clinical manifestations and inflammatory and molecular pathways with PD. We carry on hypothesizing that these similarities may be reflected in exosomal cargo modulated by the virus in correlation with disease severity. Travelling from the periphery to the brain, SARS-CoV-2-related exosomal cargo contains SARS-CoV-2 RNA, viral proteins, inflammatory mediators, and modified host proteins that could operate as promoters of neurodegenerative and neuroinflammatory cascades, potentially leading to a future parkinsonism and PD development.

Parkinsonism in viral, paraneoplastic, and autoimmune diseases.

Secondary parkinsonism, namely parkinsonism due to causes other than idiopathic neurodegeneration, may have multiple etiologies. Common secondary etiologies of parkinsonism such as drug-induced or vascular etiologies are well documented. Other secondary causes of parkinsonism such as infectious (mainly viral and prion-like diseases), autoimmune (systemic/drug-induced) and paraneoplastic etiologies are rare but are a topic of increasing interest. Older examples from the existing literature demonstrate the intricacies of viral infection from the last pandemic of the 20th century on the development of hypokinetic symptoms experienced in post-encephalitic patients. Viral and prion-like infections are only part of a complex interplay between the body's immune response and aberrant cell cycle perturbations leading to malignancy. In addition to the classic systemic autoimmune diseases (mainly systemic lupus erythematosus - SLE, and Sjögren syndrome), there have been new developments in the context of the current COVID-19 pandemic as well as more prominent use of immunotherapies such as immune checkpoint inhibitors in the treatment of solid tumors. Both of these developments have deepened our understanding of the underlying pathophysiologic process. Increased awareness and understanding of these rarer etiologies of parkinsonism is crucial to the modern diagnostic evaluation of a patient with parkinsonian symptoms as the potential treatment options may differ from the conventional levodopa-based therapeutic regimen of idiopathic Parkinson's disease. This review article aims to give an up-to-date review of the current literature on parkinsonian symptoms, their pathogenesis, diagnostic methods, and available treatment options. Many potential future directions in the field of parkinsonian conditions remain to be explored. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.

SARS-CoV-2-related encephalitis with prominent parkinsonism: clinical and FDG-PET correlates in two patients.

Considering the similarities with other pandemics due to respiratory virus infections and subsequent development of neurological disorders (e.g. encephalitis lethargica after the 1918 influenza), there is growing concern about a possible new wave of neurological complications following the worldwide spread of SARS-CoV-2. However, data on COVID-19-related encephalitis and movement disorders are still limited. Herein, we describe the clinical and neuroimaging (FDG-PET/CT, MRI and DaT-SPECT) findings of two patients with COVID-19-related encephalopathy who developed prominent parkinsonism. None of the patients had previous history of parkinsonian signs/symptoms, and none had prodromal features of Parkinson's disease (hyposmia or RBD). Both developed a rapidly progressive form of atypical parkinsonism along with distinctive features suggestive of encephalitis. A possible immune-mediated etiology was suggested in Patient 2 by the presence of CSF-restricted oligoclonal bands, but none of the patients responded favorably to immunotherapy. Interestingly, FDG-PET/CT findings were similar in both cases and reminiscent of those observed in post-encephalitic parkinsonism, with cortical hypo-metabolism associated with hyper-metabolism in the brainstem, mesial temporal lobes, and basal ganglia. Patient's FDG-PET/CT findings were validated by performing a Statistical Parametric Mapping analysis and comparing the results with a cohort of healthy controls (n = 48). Cerebrum cortical thickness map was obtained in Patient 1 from MRI examinations to evaluate the structural correlates of the metabolic alterations detected with FDG-PET/CT. Hypermetabolic areas correlated with brain regions showing increased cortical thickness, suggesting their involvement during the inflammatory process. Overall, these observations suggest that SARS-CoV-2 infection may trigger an encephalitis with prominent parkinsonism and distinctive brain metabolic alterations.

Part of the Covid19 puzzle: Acute parkinsonism.

Parkinsonism developed owing to viruses is one of the important causes of secondary parkinsonism. After the Spanish flu pandemic, the increase in the number of parkinsonian cases in the long term has drawn attention on the relationship between viruses and parkinsonism. For this reason, the relationship between influenza and parkinsonism has been studied most. Nowadays in which we are experiencing the COVID-19 pandemic, scientists, based on the experiences gained from the Spanish flu pandemic, have drawn attention to the fact that the third wave of the pandemic might be parkinsonism. However, as we have reviewed in the literature, acute parkinsonism due to COVID-19 was not reported during this pandemic. Here, we present a case in which signs of acute parkinsonism developed on the 3rd day of the illness and neurological symptoms regressed with convalescent plasma treatment.